Myeloma

Question 1

What is myeloma?

Answer 1

• malignant expansion of a clone plasma cell in BM
• Dx: >10% clonal plasma cells*
• Common in age 50+ y.o.
• CRAB symptoms

Question 2

What is a paraprotein band?

Answer 2

• aka monoclonal band or M-spike
• abnormal monoclonal band in gamma region (monoclonal gammopathy)

Question 3

What does immune paresis mean, and what is its relevance to multiple myeloma?

Answer 3

suppression of formation of the other plasma cells in the BM (& not secrete their Ig) = making them more prone to infection

Question 4

A patient with myeloma doesn’t have a monoclonal band present by serum protein electrophoresis, but urine protein electrophoresis reveals the presence of BJP, and their serum FLC ratio is abnormal. What would be the best way of monitoring this patient’s response to therapy and for any possible relapse?

Answer 4

• not detected in serum bc low MW
• use Immunofixation electrophorhesis to verify clonality (K/L ratio)

Question 5

What does the term IFE mean, and when is it used, and how is it performed?

Answer 5

• immunofixation is used for determining clonality of MM
• performed by electro -> immunofix. -> wash -> stain

Question 6

A patient has a serum protein concentration of 100 g/L. What are possible causes?

Answer 6

-Artefactual e.g. tight torniquet push H2O out of BV = inc osmolality
or due to Ig

Question 7

serum protein capillary electrophoresis: what is its advantage compared to regular agarose gel electrophoresis?

Answer 7

can quantify intact serum monoclonal proteins unlike gel electrophorhesis

Question 8

What methods are used for measurement of serum free light chains?

Answer 8

Serum LCMM: levels can be quantified & typed by immunonephlometry, immunoturbidimetry or capillary electrophorhesis

Question 9

Why do we measure the monoclonal-protein in serum by electrophoresis rather than by an immunoassay?

Answer 9

• bc have too much variation.
• have assay that’s calibrated to that Aby

Question 10

A patient is being treated with anticoagulant therapy, and another with monoclonal antibody therapy. What are possible confounding effects in the interpretation of their serum protein electrophoresis or IFE results?

Answer 10

• fibrinogen band (anticoag therapy)
• inc IgG (monoclonal therapy)
  *NOTE: use serum not plasma bc plasma contains fibrinogen = form fibrinogen band

Question 11

Common clinincal features of MM

Answer 11

C: hypercalcemia (bc osteoclast, secrete PTHrp by malignant cells)
R: renal impairment
A: Anaemia
B: Bone pain & osteolytic lesions (scans)
Others: recurrent infections, hyperviscosity
non-denatured Electrophorhesis: monoclonal band

Question 12

What is urine Bence Jones Protein (BJP)?

Answer 12

• excess free light chains (LC) in urine
• either kappa (K) or lambda type
• low MW & cleared by kidney
• can be nephrotoxic

Question 13

Alternative name for BJP in serum

Answer 13

• serum free light chain
• not usually visible by serum electrophorhesis bc low MW (but may see monoclonal band)

Question 14

What methods are used to quantify/type the Ig types: IgG, A, D, LC MM:

Answer 14

• monoclonal bands detected by urine protein electrophorhesis (UPE)
• clonality detectable by immunofixation electrophorhesis (IFE) ONLY for plasma or serum
  *non-denatured electrophorhesis

Question 15

Dx tests for MM (5)

Answer 15

1. *Detect monoclonal bands present via: serum protein electrophorhesis (SPE) & Urine protein electrophorhesis (UPE)
2. If monoclonal bands present: immunefixation electrophorhesis (IFE)
3. Detect clonality via serum K/L ratio using immunoassay: more kappa or lambda type or normal
4. FBP, ESR (viscosity in IgM), flow cytometry
5. BM aspirate/biopsy: >10% plasma cells

Question 16

prognostic test for MM

Answer 16

• cytogenetics/FISH: translocations = poor outcome
• Serum ß 2 macroglobulin/Alb. ratio & LDH: Hi elevated = poorer outcomes

Question 17

a) What’s the serum K/L ratio normal range
b) significance if outside the range

Answer 17

a) N: 0.26-1.65
b) <0.26: Lambda dominant MM
>1.65: kappa dominant MM

Question 18

Dx criteria for MM

Answer 18

1. ≥10% clonal plasma cells in BM
   AND
2. CRAB
   AND/OR
3. ≥60% clonal plasma cells in BM
   (* monoclonal band by SPE)

Question 19

What’s the dx criteria for MGUS?

Answer 19

• 50+ y.o.
• have monoclonal band w/out CRAB
• benign but need to be reviewed regularly in case it develops to smouldering myeloma -> MM

Question 20

What’s dx criteria for smouldering Myeloma?

Answer 20

• > 30g/L monoclonal band (IgM or IgG)
• Absence of CRAB or amyloidosis

Question 21

What’s Waldenstrom’s Macroglobulinaemia?

Answer 21

• Paraprotein usually IgM type
  => hyperviscosity (bc IgM)
• BJP 80% apparent

Question 22

What’s AL (amyloid LC) amyloidosis

Answer 22

• cause of amyloclonal gammopathy (abnormal band in gamma reg)
• LC amyloid deposition in tissues
• cause end organ damage

Question 23

detecting a monoclonal gammopathy (band in gamma reg) not always mean. What other conditions give a monoclonal gammopathy?

Answer 23

• monoclonal gammopathy w/ unknown significance
• smouldering myeloma
• Walsdenstrom macroglobinaemia
• Amyloid light chain (AL) amyloidosis

Question 24

T/F: A high plasma protein concentration with a normal albumin concentration represents an increase in the gamma globulin fraction

Answer 24

True bc Alb & Gamma globulin major contributors to total plasma protein